Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328270 | SCV001244355 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-25 | reviewed by expert panel | curation | The c.504delA p.(Gly169Alafs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; DOI: 10.1200/PO.16.00021). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting. |
Labcorp Genetics |
RCV000204728 | SCV000261598 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly169Alafs*46) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 220776). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002336568 | SCV002641867 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-14 | criteria provided, single submitter | clinical testing | The c.504delA pathogenic mutation, located in coding exon 4 of the CDH1 gene, results from a deletion of one nucleotide at nucleotide position 504, causing a translational frameshift with a predicted alternate stop codon (p.G169Afs*46). This alteration has been reported in a family meeting International Gastric Cancer Linkage Consortium (IGCLC) guidelines for hereditary diffuse gastric cancer (HDGC) (Lowstuter K et al. JCO Precision Oncology, 2017 Mar;1,1-12). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV000204728 | SCV004043119 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-09 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Clinical Genetics Laboratory, |
RCV004696870 | SCV005197407 | pathogenic | not provided | 2024-03-18 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004767151 | SCV005381663 | pathogenic | Malignant tumor of breast | 2024-08-01 | criteria provided, single submitter | clinical testing | Variant summary: CDH1 c.504delA (p.Gly169AlafsX46) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251348 control chromosomes. c.504delA has been reported in the literature in individual(s) affected with Breast Cancer (e.g. Adib_2022). The following publication have been ascertained in the context of this evaluation (PMID: 34949788). ClinVar contains an entry for this variant (Variation ID: 220776). Based on the evidence outlined above, the variant was classified as pathogenic. |
Genome |
RCV000204728 | SCV004228866 | not provided | Hereditary diffuse gastric adenocarcinoma | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 02-23-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |